US3781311A - Novel preparation of trienic steroids - Google Patents
Novel preparation of trienic steroids Download PDFInfo
- Publication number
- US3781311A US3781311A US00213731A US3781311DA US3781311A US 3781311 A US3781311 A US 3781311A US 00213731 A US00213731 A US 00213731A US 3781311D A US3781311D A US 3781311DA US 3781311 A US3781311 A US 3781311A
- Authority
- US
- United States
- Prior art keywords
- seco
- ethyl
- gonadiene
- carbon atoms
- bis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000002360 preparation method Methods 0.000 title abstract description 9
- 150000003431 steroids Chemical class 0.000 title abstract description 7
- 238000000034 method Methods 0.000 abstract description 18
- 239000000543 intermediate Substances 0.000 abstract description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 125000004432 carbon atom Chemical group C* 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- -1 isobutenyl Chemical group 0.000 description 9
- JOXIMZWYDAKGHI-UHFFFAOYSA-N p-toluenesulfonic acid Substances CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
- 238000005903 acid hydrolysis reaction Methods 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 150000001340 alkali metals Chemical class 0.000 description 5
- 238000005907 ketalization reaction Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 235000018734 Sambucus australis Nutrition 0.000 description 4
- 244000180577 Sambucus australis Species 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 150000002902 organometallic compounds Chemical class 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000003828 vacuum filtration Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- XTTGBNFBLKGXTM-HWSKEQOTSA-N (9r,10s,13s)-13-methyl-2,3,4,5,6,7,9,10,11,12-decahydro-1h-cyclopenta[a]phenanthren-17-one Chemical compound C([C@@H]1[C@H]2CC3)CCCC1CCC2=C1[C@@]3(C)C(=O)C=C1 XTTGBNFBLKGXTM-HWSKEQOTSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- CIHXIRAAMAUYLZ-UHFFFAOYSA-N [K+].[K+].[C-]#[C-] Chemical compound [K+].[K+].[C-]#[C-] CIHXIRAAMAUYLZ-UHFFFAOYSA-N 0.000 description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 125000000962 organic group Chemical group 0.000 description 2
- 125000002524 organometallic group Chemical group 0.000 description 2
- 125000005489 p-toluenesulfonic acid group Chemical group 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 125000000547 substituted alkyl group Chemical group 0.000 description 2
- 238000002211 ultraviolet spectrum Methods 0.000 description 2
- HWCYISVQOIISSU-HULBTWJISA-N (8R,9R,10S,13R)-13-methyl-1,2,3,4,5,6,7,8,9,10,11,12-dodecahydrocyclopenta[a]phenanthrene Chemical compound C([C@@H]12)CCCC1CC[C@@H]1[C@@H]2CC[C@@]2(C)C1=CC=C2 HWCYISVQOIISSU-HULBTWJISA-N 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- WRFWAYDBNCOWRA-UHFFFAOYSA-N 3,4-dichloro-1-(6-iodo-4-oxo-2-thiophen-2-ylquinazolin-3-yl)pyrrole-2,5-dione Chemical compound O=C1C(Cl)=C(Cl)C(=O)N1N1C(=O)C2=CC(I)=CC=C2N=C1C1=CC=CS1 WRFWAYDBNCOWRA-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000002641 lithium Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- YSQFBLFEYNOIBW-UHFFFAOYSA-N lithium;cyclopropane Chemical compound [Li+].C1C[CH-]1 YSQFBLFEYNOIBW-UHFFFAOYSA-N 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 125000005394 methallyl group Chemical group 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/72—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 spiro-condensed with carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/16—Benz[e]indenes; Hydrogenated benz[e]indenes
Definitions
- the novel process for the preparation of ,trienic steroids of the formula o wherein R is alkyl of 1 to 4 carbon atoms and X is selected from the group consisting of aliphatic of 1 to 6 carbon atoms optionally substituted and cycloalkyl of 3 to 6 carbon atoms comprises reacting 13B-R-4,5-seco- A -gonadiene-3,5,17-trione wherein R is alkyl of 1 to 4 carbon atoms with ethylene glycol in the presence of an acidic catalyst to selectively form 3,5-bis-ethylenedioxyl3fl-R-4,5-seco-A -gonadiene-17-one, reacting the latter with an organo-metallic.
- organo is X as defined above to form 3,5-bis-ethylenedioxy-13B- R-l7a-X-4,5-seco A gonadiene-l7fi-ol, subjecting the latter to acid hydrolysis to form 13/3-R-17u-X4,5-seco- A -gonadiene-17,3-ol-3,5-dione and cyclizing the latter with a basic agent to form the corresponding 1313-R-l7a- X-A -gonatriene-17 8-o1-3-one.
- R is preferably alkyl of 1 to 4 carbon atoms such as methyl, ethyl, propyl, isopropyl or butyl and X is preferably a saturated or unsaturated aliphatic radical optionally substituted such as methyl, ethyl, propyl, isopropyl, vinyl, allyl, 2-methylallyl, isobutenyl, ethynyl, l-propynyl, 2-propynyl, 2- butynyl, butadienyl, chloroethynyl or trifluoropropynyl or a cycloalkyl of 3 to 6 carbon atoms such as cyclopropyl, cyclopentyl or cyclohexyl.
- X is preferably a saturated or unsaturated aliphatic radical optionally substituted such as methyl, ethyl, propyl, isopropyl, vinyl, allyl, 2-methylallyl, iso
- the ketalization of the 3 and S-keto groups with ethylene glycol is selective so that the 17-keto group is not ketalized.
- the acidic catalyst is preferably p-toluene sulfonic acid and the ketalization is preferably effected in the presence of a lower alkyl orthoformate such as ethyl orthoformate.
- This selective ketalization is remarkable because it is effected under mild conditions in excellent yields while the ketalization of the 3-keto group of 11 g0natriene-3,l7-dione, a completely cyclized compound, as described in French Pat. No. 1,492,782 results in mediocre yields of 50 to 60%.
- the reaction is preferably effected at room temperature for a suflicient period for the keto in the 3 and S-positions to both react.
- the organo-metallic compound is preferably an organomagnesium halide such as chloride, bromide or iodide or an organo alkali metal compound of the formula XM wherein X is as defined above and M is an alkali metal such as lithium, sodium or potassium.
- the acid hydrolysis may be effected with an inorganic acid such as hydrochloric acid or sulfuric acid or an organic acid such as acetic acid, citric acid or p-toluene sulfonic acid.
- the hydrolysis may be effected in one or more solvents such as alkanols such as methanol, ethanol or isopropanol, ketones such as acetone or a hydrocarbon such as benzene or toluene.
- the basic agent for the cyclization is preferably a strong base.
- alkali metal alcoholates such as sodium methylate, sodium ethylate, sodium or potassium tert-butylate or potassium teramylate or an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide.
- the 13B-R-4,5-seco-A -gonadiene-3,5,17-triones used as starting materials can be prepared by dehydration of the corresponding 13 ⁇ ? R 4,5 seco A -gonene-1 113-01- 3,5,17-trione with a dehydrating agent such as sulfuric acid.
- the starting gonadiene was prepared as follows:
- Step B.3,5 bis-ethylenedioxy-13fi-ethyl-17a-ethynyl- 4,5 seco A -gonadiene-17B-ol 7.5 gm. of potassium terbutylate were introduced into 50 ml. of tetrahydrofuran and acetylene was bubbled therethrough for 30 minutes, 5 gm. of 3,5-bis-ethylenedioxy-l3/3-ethyl-4,5, seco- A -gonadiene-17-one were added and the mixture was agitated for 1% hours at 20 C. with acetylene bubbling. The resulting suspension was poured into an aqueous solution of ammonium chloride and the mixture was agitated.
- Step C.l3,B ethyl-17a-ethynyl-4,5-seco-A -gonadiene-17B-ol3,5-dione 5 gm. of 3,5-bis-ethylenedioxy-13 8- ethyl-17a-ethynyl-4,5-seco-A -gonadiene-1718-01 were introduced into ml. of acetone and after 7.5 ml. of an aqueous solution of about 3 N-hydrochloric acid were added, the mixture was agitated for 2 hours at C. The resulting solution was poured into a water-ice mixture and agitated. The formed precipitate was isolated by vacuum filtration, was washed and dried to obtain 3.6 gm.
- Step D.-13,6 ethyl-17ot-ethynyl-4,9,l1-gonatriene-17B- ol-3-one In an inert atmosphere, 3 gm. of 13fi-ethyl-l7aethynyl 4,5-seco-A -gonadiene 17B-ol-3,5-dione were dissolved in 15 ml. of methanol, and then 5.4 ml. of a 10% methanol solution of potassium hydroxide were slowly introduced. The resulting solution was refluxed for 2 hours and then cooled. 0.5 ml. of acetic acid were added, and the reaction solution was poured in a waterice mixture, cooled, and agitated. The formed precipitate was isolated by vacuum filtration, and was washed and dried to obtain 2.83 gm. of crude product melting at 148 C.
- the starting estradiene is obtained from 4,5-seco-A estrene-l15-ol-3,5,17-trione by a process analogous to the one described at stage A of Example I.
- EXAMPLE v EXAMPLE VI 3,5-bis-ethylenedioxy-4,S-seco A estradiene 17- one was reacted with cyclopropyl lithium to form 3,5- bis-ethylenedioxy-l7a-cyclopropyl-4,5-seco A estradienediene-17/3-ol 01 which was subjected to acid hydrolysis to form 17ut-cyclopropyl-4,5-seco-A"' estradiene- 17fl-ol-3,5-dione. The said product was cyclized to form 17a-cyclopropropyl-A estratriene-l7p-ol-3-one.
- R is alkyl of 1 to 4 carbon atoms and X is selected from the group consisting of aliphatic of 1 to 6 carbon atoms optionally substituted with halogen and cycloalkyl of 3 to 6 carbon atoms comprising reacting 13fl-R-4,5-seco-A -gonadiene-3,5,l7-trione wherein R is alkyl of 1 to 4 carbon atoms with ethylene glycol in the presence of an acidic catalyst to selectively form 3,5-bisethylenedioxy-13fl-R-4,5-seco-A -gonadiene 17 one, reacting the latter with an organo-metallic compound wherein the organo is X as defined above to form 3,5- bis-ethylenedioxy-l3B-R-17m-X-4,5-seco-A gonadiene- 17 3-01, subjecting the latter to acid hydrolysis to form l3 3-R-17a-X-4,5-seco-A -gonadiene-1713-01 3,5 dionc and cyclizing the organ
- organo-metallic agent is selected from the group consisting of XMgHal wherein X has the definition of claim 1 and Hal is selected from the group consisting of chlorine, bromide and iodine and XM wherein M is an alkali metal.
- a process for the preparation of 13fl-ethyl-17aethynyl-A -gonatriene--01-3 comprising reacting 13fl-ethyl-4,5-sec0-A -gonadiene-3,5,l7-tri0ne with ethylene glycol in the presence of p-toluene sulfonic acid and ethyl orthoformate to selectively form 3,5-bis-ethylenedioxy-13;8-ethyl-4,5-seco-A"- gonadiene 17 one, reacting the latter with potassium acetylide to form 3,5- bis-ethylenedioxy-13fl-ethyl-17u-ethynyl-4,5 seco A gonadiene-17 fl-ol, reacting the latter with hydrochloric acid to form 13,3-ethyl-17a-ethynyl-4,5-seco-A gonadiene- 17fl-ol-3,5-dione and cyclizing the latter
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7109709A FR2129895B1 (enrdf_load_stackoverflow) | 1971-03-19 | 1971-03-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3781311A true US3781311A (en) | 1973-12-25 |
Family
ID=9073817
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US00213731A Expired - Lifetime US3781311A (en) | 1971-03-19 | 1971-12-29 | Novel preparation of trienic steroids |
Country Status (19)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4333928A (en) * | 1979-05-17 | 1982-06-08 | Schering, Aktiengesellschaft | 16 α-Alkyl steroids, their preparation, and pharmaceutical preparations thereof |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL51468A (en) * | 1976-02-23 | 1981-01-30 | Sparamedica Ag | 17 -hydroxy- -d-homosteroid derivatives,their preparation and pharmaceutical compositions containing them |
| JPS5387730U (enrdf_load_stackoverflow) * | 1976-12-21 | 1978-07-19 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL130550C (enrdf_load_stackoverflow) * | 1966-05-26 |
-
1971
- 1971-03-19 FR FR7109709A patent/FR2129895B1/fr not_active Expired
- 1971-12-29 US US00213731A patent/US3781311A/en not_active Expired - Lifetime
-
1972
- 1972-03-02 IL IL38871A patent/IL38871A/xx unknown
- 1972-03-02 IL IL46789A patent/IL46789A/en unknown
- 1972-03-07 CH CH332072A patent/CH551961A/fr not_active IP Right Cessation
- 1972-03-09 ZA ZA721620A patent/ZA721620B/xx unknown
- 1972-03-15 CA CA137,199A patent/CA971159A/en not_active Expired
- 1972-03-15 DE DE2212589A patent/DE2212589C3/de not_active Expired
- 1972-03-16 BE BE780811A patent/BE780811A/xx not_active IP Right Cessation
- 1972-03-17 GB GB1257972A patent/GB1355454A/en not_active Expired
- 1972-03-17 SU SU1758226A patent/SU422142A3/ru active
- 1972-03-17 DD DD161626A patent/DD95230A5/xx unknown
- 1972-03-17 JP JP47026715A patent/JPS517665B1/ja active Pending
- 1972-03-17 HU HURO650A patent/HU163771B/hu unknown
- 1972-03-17 AU AU40116/72A patent/AU471391B2/en not_active Expired
- 1972-03-17 SE SE7203508A patent/SE385012B/xx unknown
- 1972-03-17 NL NL7203577.A patent/NL157314B/xx not_active IP Right Cessation
- 1972-03-20 AT AT234872A patent/AT316766B/de not_active IP Right Cessation
- 1972-03-20 DK DK129172AA patent/DK130308B/da not_active IP Right Cessation
- 1972-03-20 IE IE348/72A patent/IE36180B1/xx unknown
-
1975
- 1975-07-31 SE SE7508689A patent/SE409210B/xx not_active IP Right Cessation
-
1978
- 1978-05-31 SE SE7806349A patent/SE418747B/sv not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4333928A (en) * | 1979-05-17 | 1982-06-08 | Schering, Aktiengesellschaft | 16 α-Alkyl steroids, their preparation, and pharmaceutical preparations thereof |
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